Evidence map›Paper›PMID 28874829›Full record

ArticleScientific reports2017

Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.

Katherine E Larrimore, I Can Kazan, Latha Kannan, R Player Kendle, Tameem Jamal, Matthew Barcus, Ashini Bolia, Stephen Brimijoin, Chang-Guo Zhan, S Banu Ozkan and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 38 citations in OpenAlex.

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  7. Engineering gain-of-function mutants of a WW domain by dynamics and structural analysis.Protein science : a publication of the Protein Society · 2023
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  8. Allosteric regulatory control in dihydrofolate reductase is revealed by dynamic asymmetry.Protein science : a publication of the Protein Society · 2023
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  16. Ancient thioredoxins evolved to modern-day stability-function requirement by altering native state ensemble.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 2 countries.

Katherine E LarrimoreSchool of Life Sciences and Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, 85287-4501, USA.
I Can KazanDepartment of Physics and Center for Biological Physics, Arizona State University, Tempe, AZ, 85287-1504, USA.
Latha KannanSchool of Life Sciences and Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, 85287-4501, USA.
R Player KendleSchool of Life Sciences and Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, 85287-4501, USA.
Tameem JamalSchool of Life Sciences and Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, 85287-4501, USA.
Matthew BarcusSchool of Life Sciences and Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, 85287-4501, USA.
Ashini BoliaDepartment of Physics and Center for Biological Physics, Arizona State University, Tempe, AZ, 85287-1504, USA.
Stephen BrimijoinDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
Chang-Guo ZhanMolecular Modeling and Biopharmaceutical Center and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA.
S Banu OzkanDepartment of Physics and Center for Biological Physics, Arizona State University, Tempe, AZ, 85287-1504, USA.
Tsafrir S MorSchool of Life Sciences and Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, 85287-4501, USA. tsafrir.mor@asu.edu.ORCID 0000-0002-6123-6194
Arizona State University · USARUP Laboratories (United States) · USCornell University · USMayo Clinic · USTemasek Life Sciences Laboratory · SGUniversity of Kentucky · USUniversity of Wisconsin–Madison · US

Funding

Cocaine hydrolase gene therapy for cocaine abuse (DPI)DP1DA031340 · NIDA · MAYO CLINIC ROCHESTER · PI BRIMIJOIN, WILLIAM STEPHEN · 2010 to 2014
$3.9M
NIDA NIH HHS DP1 DA031340
6 · The paper itself

Abstract

Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme's ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in plants and their enzymatic properties were investigated. In particular, we explored the effects that these site-directed mutations have over the enzyme kinetics with various substrates of BChE. We further compared the affinity of various anticholinesterases including organophosphorous nerve agents and pesticides toward these BChE variants relative to the wild type enzyme. In addition to serving as a therapy for cocaine addiction-related diseases, enhanced bioscavenging against other harmful agents could add to the practicality and versatility of the plant-derived recombinant enzyme as a multivalent therapeutic.

Indexed as

Plant ProteinsRecombinant ProteinsAllosteric RegulationBinding SitesButyrylcholinesteraseCatalytic DomainCholinesterase InhibitorsCocaineGenetic VariationHydrolysisMutationProtein BindingStereoisomerismButyrylcholinesteraseCholinesterase InhibitorsCocainePlant ProteinsRecombinant Proteins

Identifiers

PMID28874829
PMCPMC5585256
OpenAlexW2752784998

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.